A1C Between 5.7 and 6.4% as a Marker for Identifying Pre-Diabetes, Insulin Sensitivity and Secretion, and Cardiovascular Risk Factors

OBJECTIVE A1C is an optional method for diagnosing diabetes and also for detecting individuals at increased risk of the disease. However, how A1C compares with fasting (FPG) and 2-h plasma glucose for detecting at-risk individuals is not well known. RESEARCH DESIGN AND METHODS A 2-h glucose tolerance test, frequently sampled intravenous glucose tolerance test, and A1C were obtained at the follow-up examination in 855 participants in the Insulin Resistance Atherosclerosis Study (IRAS). For this report, 385 individuals were at increased risk of diabetes as defined by A1C between 5.7 and 6.4%, impaired glucose tolerance (IGT), and/or impaired fasting glucose (IFG). RESULTS IFG and IGT identified 69.1 and 59.5% of all individuals at increased risk of diabetes, respectively. A1C 5.7-6.4% detected 23.6% of all at-risk individuals, although more African Americans (31.4%) and Hispanics (35.2%) than non-Hispanic whites (9.9%). Relative to A1C, FPG was more strongly related to fasting insulin (r = 0.38 vs. 0.26; P < 0.01), acute insulin response (r = - 0.20 vs. - 0.09; P < 0.01), and waist circumference (r = 0.43 vs. 0.25; P < 0.001) by the Spearman correlation test. Similarly, 2-h plasma glucose was more strongly related to Si (r = - 0.40 vs. - 0.27; P < 0.01) and triglycerides (r = 0.30 vs. 0.08; P < 0.001). CONCLUSIONS A1C 5.7-6.4% is less sensitive for detecting at-risk individuals than IFG and IGT, particularly among non-Hispanic whites. Single determinations of FPG and 2-h plasma glucose seem to be more precise correlates of insulin resistance and secretion than A1C and, in general, better for other metabolic disorders.